固相片段法合成利拉鲁肽  

Study on the solid-phase synthetic process of liraglutide

作　　者：王硕冰 郝星宇 王恩慧 王钝[2] WANG Shuo-bing;HAO Xing-yu;WANG En-hui;WANG Dun(College of Pharmacy,Harbin University of Commerce,Harbin 150076,China;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]哈尔滨商业大学药学院,黑龙江哈尔滨150076 [2]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2023年第5期339-346,共8页Chinese Journal of Medicinal Chemistry

摘　　要：目的 研究利拉鲁肽的固相合成。方法 通过汇聚式合成策略,利用固相片段缩合法制备利拉鲁肽。以芴甲氧羰基(Fmoc)保护的氨基酸为原料,分别合成4个全保护多肽片段,依照肽序依次偶联得到全保护利拉鲁肽主链[GLP-1(7-37)],经缩合反应在第20位赖氨酸引入侧链Nα-棕榈酰基-L-谷氨酰基,最后将其从树脂上切割并脱保护得到利拉鲁肽。结果与结论利拉鲁肽粗肽收率为25.65%,纯度为52.35%。采用制备型反相高效液相色谱技术进行分离纯化后,利拉鲁肽纯度为98.42%。该合成工艺反应条件温和、操作简单、合成周期短,是实验室规模下较好的利拉鲁肽制备方法。Liraglutide is a human glucagon-like peptide-1(GLP-1) receptor agonist developed by Novo Nordisk.In this study, the total synthesis of the antidiabetic peptide liraglutide was described.Liraglutide was synthesized via a convergent approach from four peptide fragments prepared by Fmoc-strategy solid phase peptide synthesis(SPPS).The synthetic process has many advantages such as mild reaction condition, synthetic feasibility as well as acceptable yield.This study provides a practical preparative process of liraglutide on lab scale.

关 键 词：利拉鲁肽 人胰高血糖素样肽-1 多肽固相片段缩合 多肽固相合成 

分 类 号：R914[医药卫生—药物化学]